CN101619058A - Benzimidazole-4-acid amide type derivant - Google Patents

Benzimidazole-4-acid amide type derivant Download PDF

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CN101619058A
CN101619058A CN200910045056A CN200910045056A CN101619058A CN 101619058 A CN101619058 A CN 101619058A CN 200910045056 A CN200910045056 A CN 200910045056A CN 200910045056 A CN200910045056 A CN 200910045056A CN 101619058 A CN101619058 A CN 101619058A
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benzoglyoxaline
hnmr
acid
coor
benzimidazole
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罗先金
张钟闾
薛飞
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Shanghai Jiaotong University
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Shanghai Jiaotong University
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Priority to CN200910045056A priority Critical patent/CN101619058A/en
Priority to CN2010100000501A priority patent/CN101941973A/en
Priority to AU2010204407A priority patent/AU2010204407A1/en
Priority to PCT/CN2010/000024 priority patent/WO2010078830A1/en
Priority to EP15177286.0A priority patent/EP2963033B1/en
Priority to KR1020117018492A priority patent/KR20110124751A/en
Priority to EP20100729089 priority patent/EP2386553A4/en
Priority to JP2011544774A priority patent/JP2012514607A/en
Priority to RU2011133009/04A priority patent/RU2558328C2/en
Priority to CA2749174A priority patent/CA2749174C/en
Priority to US13/143,731 priority patent/US8871946B2/en
Publication of CN101619058A publication Critical patent/CN101619058A/en
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Abstract

The invention discloses a benzimidazole-4-acid amide type derivant, a structural formula of which is shown in a right picture, wherein X is alkyl and aryl or heterocyclic radical, and Y is hydrogen radical, alkyl, alkenyl, cycloalkyl and aryl or heterocyclic radical. The invention has good antiviral effect.

Description

A kind of benzoglyoxaline-4-acidamide type derivative
Technical field:
The present invention relates to a kind of organic compound, particularly a kind of benzoglyoxaline-4-acidamide type derivative, they have good Antipicornaviral performance, can be applicable to the development of antiviral.
Background technology:
Disease of viral infection serious threat human health and life have become a great problem of medical circle, and according to statistics, epidemic infectious diseases nearly 70% is caused by virus infection.The transmissible disease that is caused by enterovirus (enteroviruses) worldwide happens occasionally.The enterovirus genus Picornaviridae, comprise poliovirus (Polio viruses), Coxsackie virus (Cosxackie viruses), EHCO virus (Entericcytopathogenic human orphan virus) and new enterovirus (New enteroviruses), every viroid has multiple serotype, have at least more than 70 types, invade multiple tissue,, cause multiple communicable disease in the whole world as nerve, cardiac muscle, muscle, skin and eye conjunctiva etc.The Coxsackie virus classification is more, and its route of transmission and pathogenic course are similar to poliovirus, see with inapparent infection more.Show as the slight symptoms such as sense or diarrhoea that go up, can invade central nervous system once in a while, infringement ventricornu motor nerve cells cause the slowness limb paralysis, but symptom are generally lighter.Coxsackie virus can be invaded multiple tissue system, as respiratory tract, enteron aisle, skin, muscle, heart, liver, suprarenal gland and central nervous system, causes the clinical manifestation variation.Clinical commonly have: the hot fash of (1) respiratory tract infection (2) herpangina (3) (4) hand foot mouth disease (5) infantile diarrhea (6) central nervous system syndromes (7) myocarditis and pericarditis (8) epidemic pleurodynia or myalgia (9) epidemic conjunctivitis (10) Coxsackie virus hepatitis (11) other.
Our former research Bioorganic and Medicinal Chemistry Letters (2005,15:267-269), find that following structural series compound has good anti-Coxsackie virus effect among the ZL 200410084296.6.
Figure A20091004505600051
In the formula: X is
Figure A20091004505600052
Y is
Figure A20091004505600061
-CH 2CH 2OH or
Figure A20091004505600062
Wherein, R can represent F, Cl, Br, CH respectively 3, OH, NO 2Or H.
In the patent 200810040925.3 of application in early stage
Figure A20091004505600063
In the formula: X is F, Cl, Br, CH 3, OH, NO 2Or H;
Y be H,
Figure A20091004505600064
Wherein R is F, Cl, Br, CH 3, OH, NO 2Or H.
In the patent 200810042783.4 of application,
Figure A20091004505600065
In the formula: X is
Y be H,
Figure A20091004505600067
R wherein 1Be F, Cl, Br, CH 3, OH, NO 2Or H;
R 2Be F, Cl, Br, CH 3, OH, NO 2Or H.
In the patent 200810042790.4 of application in early stage,
Figure A20091004505600071
In the formula: X is
Figure A20091004505600072
Y be H,
Wherein R is F, Cl, Br, CH 3, OH, NO 2Or H.
J.Med.Chem. (1990,33:814-819) reported the series compound of following structure, and pointed out that it has the potential antitumous effect.
Figure A20091004505600074
In the formula: R is
Figure A20091004505600075
Report has synthesized the series compound of following structure among the patent US6100283, and points out that they are good PARP[poly (ADP-ribose) polysaccharases] inhibitor, have good anticancer effect.
Figure A20091004505600076
Summary of the invention:
The structural formula of a kind of benzoglyoxaline of the present invention-4-acidamide type derivative is as follows:
Figure A20091004505600081
Wherein:
X is alkyl, aryl or heterocyclic radical;
Y is hydrogen, alkyl, cycloalkyl, aryl or heterocyclic radical.
A kind of benzoglyoxaline of the present invention-4-acidamide type derivative, X and Y in its structural formula are as follows:
X is:
Figure A20091004505600082
N=0-5 wherein,
R 1, R 2, R 3, R 4And R 5Be respectively H, CH 3, F, Cl, Br, I, OR 6, NO 2, Or
Figure A20091004505600092
R wherein 6Be H, CH 3Or CH 2CH 3, R 7And R 8Be respectively H, CH 3, CH 2CH 3Or CH 2CH 2OH, Ra 1, Ra 2, Ra 3, Ra 4And Ra 5Be respectively F, Cl, Br, I, CH 3, CH 2CH 3, ORa, CH 2CH 2OH, NO 2, N (Rb) 2, CN or COORc, wherein Ra is H, CH 3Or CH 2CH 3, Rb is H, CH 3, CH 2CH 3Or CH 2CH 2OH, Rc are H, CH 3, CH 2CH 3Or C 6H 5,
R 9, R 10, R 11, R 12And R 13Be respectively H, CH 3, CH 2CH 3, COOR 14, OR 15, CN, F, Cl, Br, I or N (R 16) 2, R wherein 14, R 15And R 16Be respectively H, CH 3Or CH 2CH 3,
R 17, R 18, R 19, R 20, R ' 17, R ' 18, R ' 19, R ' 20, R " 17, R " 18, R " 19And R " 20Be respectively H, CH 3, CH 2CH 3, OR 21, CF 3, CCl 3, CBr 3, N (R 22) 2, NO or NO 2, R wherein 21Be H, CH 3Or CH 2CH 3, R 22Be H, CH 3, CH 2CH 3Or CH 2CH 2OH,
R 23, R 24, R 25, R ' 23, R ' 24And R ' 25Be respectively H, CH 3, CH 2CH 3, F, Cl, Br, I, OR 26, NO 2, N (R 27) 2Or COOR 28, R wherein 26And R 28Be respectively H, CH 3, CH 2CH 3, R 27Be H, CH 3, CH 2CH 3, CH 2CH 2OH,
R 29, R 30, R 31And R 32Be respectively H, CH 3, CH 2CH 3, OCH 3, CH 2OH, NO 2Or N (R 33) 2, R wherein 33Be respectively H, CH 3, CH 2CH 3Or CH 2CH 2OH,
R 34And R 36Be respectively H, (CH 2) nCH 3, CH 2OH, CH 2CH 2OH, CH (CH 3) 2Or CH 2CH (OH) CH 3, n= 0- 5, R 35, R 37And R 38Be respectively H, CH 3, CH 2CH 3, OCH 3, CH 2OH, NO 2Or N (R ' 33) 2, R ' wherein 33Be H, CH 3, CH 2CH 3Or CH 2CH 2OH,
R 39, R 40, R 42And R 43Be respectively H, CH 3, CH 2CH 3, OCH 3, CH 2OH, NO 2Or N (R " 33) 2, R wherein " 33Be H, CH 3, CH 2CH 3Or CH 2CH 2OH, R 41Be H, (CH 2) nCH 3, CH 2OH, CH 2CH 2OH or CH 2CH (OH) CH 3, n=0-5,
Z is N, O, S, R 44, R 45, R 46, R ' 44, R ' 45And R ' 46Be respectively H, CH 3, CH 2CH 3, OR 47, NO 2, N (R 48) 2, CN or COOR 49, R wherein 47And R 49Be respectively H, CH 3Or CH 2CH 3, R 48Be H, CH 3, CH 2CH 3Or CH 2CH 2OH,
Rs 1, Rs 2, R ' s 1And R ' s 2Be respectively H, CH 3, CH 2CH 3, N (R ') 2, F, Cl, Br, I or NHCOR ", wherein R ' is H, CH 3, CH 2CH 3Or CH 2CH 2OH, R " is CH 3, CH 2CH 3Or C 6H 5,
Rm 1, Rm 2, Rm 3, R ' m 1, R ' m 2Or R ' m 3Be H, CH 3, CH 2CH 3, F, Cl, Br, OH, N (Rm) 2Or C 6H 5, wherein Rm is H, CH 3, CH 2CH 3, CH 2CH 2OH;
Y is
Figure A20091004505600093
Wherein
R 50, R 51, R 52, R 53, R 54, R 55, R 56, R 57, R 58, R 59, R 60, R 61, R 62, R 63, R 64, R 65, R 66, R 67, R 68, R 69, R 70, R 71, R 72And R 73Be respectively H, CH 3, CH 2CH 3, CH 2OH, OR 74, CN, NO 2, N (R 75) 2, F, Cl, Br or
Figure A20091004505600101
R wherein 74Be H, CH 3Or CH 2CH 3, R 75Be H, CH 3, CH 2CH 3Or CH 2CH 2OH, R 76Be respectively H, CH 3, OH, NO 2, NH 2,
R 77, R 78, R 79, R 80And R 81Be respectively H, CH 3, CH 2CH 3, OR 82, NO 2, CN, COOR 83, F, Cl, Br, CF 3, CCl 3, N (R 84) 2, R wherein 82With R83Be respectively H, CH 3, CH 2CH 3, R 84Be H, CH 3, CH 2CH 3, CH 2CH 2OH,
R 85, R 86And R 87Be respectively H, CH 3, CH 2CH 3, OH or NH 2,
Q is N, O or S, R 88, R 89, R 90, R ' 8 8, R ' 89And R ' 90Be respectively H, CH 2CH 3, OR 91, NO 2, N (R 92) 2, CN, COOR 93, R wherein 91And R 93Be respectively H, CH 3, CH 2CH 3, R 92Be H, CH 3, CH 2CH 3Or CH 2CH 2OH,
R 94, R 95, R ' 94And R ' 95Be respectively H, CH 3, CH 2CH 3, N (R 96) 2, F, Cl, Br, I or NHCOR 97, R wherein 96Be H, CH 3, CH 2CH 3Or CH 2CH 2OH, R 97Be CH 3, CH 2CH 3Or C 6H 5
A kind of benzoglyoxaline of the present invention-4-acidamide type derivative has:
The anti-coxsackie B 3 virus activity results of compound of the present invention's preparation are as shown in the table:
Figure A20091004505600161
In the table: "-" expression sample is at maximal non-toxic dosage nonreactive coxsackie B 3 virus activities.
IC 50Expression is to viral half-inhibition concentration.
RBV is a ribavirin, claims ribavirin (Ribavirin) again, virazole
By detected result as can be seen, this series compound has anti-preferably coxsackie B 3 viral performances.
The preparation method of the present invention-kind of benzoglyoxaline-4-acidamide type derivative is as follows:
With 2-glycyl-3-nitrobenzoic acid is starting raw material; process ammonia is separated, Hoffman degrades, reduction preparation 2; the 3-diaminobenzoic acid; then 2; the condensation under the neutralized verdigris effect of 3-diaminobenzoic acid and aldehyde compound makes benzoglyoxaline-4-carboxylic acid; benzoglyoxaline-4-carboxylic acid and thionyl chloride effect obtain acyl chlorides, again with amine condensation prepared target product benzoglyoxaline-4-acidamide type derivative.
Description of drawings:
Fig. 1 is 2-(2,3,4-trihydroxy-the phenyl)-1H-benzoglyoxaline-4-carboxylic acid of embodiment 9 preparation 1HNMR figure.
Fig. 2 is 2-(5-nitro-2-furyl)-1H-benzoglyoxaline-4-(N-(1-methylol-2-p-nitrophenyl hydroxyethyl)) acid amides of embodiment 16 preparation 1HNMR figure.
Fig. 3 is (L)-2-(2-pyridyl)-1H-benzoglyoxaline-4-(N-(1-methylol-2-p-nitrophenyl hydroxyethyl)) acid amides of embodiment 21 preparation 1HNMR figure.
Fig. 4 is 2-(4-hydroxy phenyl)-1H-benzoglyoxaline-4-(the adjacent fluorophenyl of N-) acid amides of example 22 preparation 1HNMR figure.
Fig. 5 is (L)-2-(3-hydroxy phenyl)-1H-benzoglyoxaline-4-(N-(1-methylol-2-p-nitrophenyl hydroxyethyl)) acid amides of embodiment 23 preparation 1HNMR figure.
Fig. 6 is 2-(5-nitro-2-furyl)-1H-benzoglyoxaline-4-(the adjacent fluorophenyl of N-) acid amides of embodiment 26 preparation 1HNMR figure.
Specific implementation method:
Embodiment 1:2,3-diaminobenzoic acid synthetic
The first step, 2-glycyl-3-nitrobenzoic acid synthetic
The adjacent dibenzoic acid acid anhydride of 30 gram 3-nitros is joined in the strong aqua of 45ml, heating, insulation, needle crystal is separated out in cooling.Acidifying gets white solid, filters, and drying obtains product 2-glycyl-3-nitrobenzoic acid 29.4g.
Second step, 2-amino-3-nitrobenzoic acid synthetic
13.9 gram bromines are splashed in the aqueous solution of 100ml of 7.3 gram sodium hydroxide.Add 17 gram 2-glycyl-3-nitrobenzoic acids then.Heating, reaction system is separated out a large amount of red solid.Filter, acidifying obtains yellow product, and is dry that 2-amino-3-nitrobenzoic acid 13.7 restrains.Thick product can get yellow needle-like crystal with the hot water recrystallization.
The 3rd step, 2,3-diaminobenzoic acid synthetic
3 gram 2-amino-3-nitrobenzoic acids are joined in the methyl alcohol of 30ml, splash into equimolar 20% aqueous sodium hydroxide solution, raw material is dissolved fully, add the Raney Ni of 0.2 gram, reflux.Splash into 80% hydrazine hydrate (about 1.5eq * 1.1) then to yellow completely dissolve, filtered while hot is fallen Raney Ni.Mother liquor concentrates acidifying redness 2,3-diaminobenzoic acid 2.3 grams.Thick product can further separate purification with column chromatography.
Synthesizing of embodiment 2:2-(5-nitro-2-furyl)-1H-benzoglyoxaline-4-carboxylic acid
With 2, the 3-diaminobenzoic acid is dissolved in the methyl alcohol, under agitation the methanol solution of Dropwise 5-nitryl furfural.Then with neutralized verdigris (Cu (Ac) 2H 2O) the aqueous solution splashes in the top reaction system, reflux.Filtered while hot, the mixed solution dissolving filter cake splashes into sodium sulfide solution, is heated to boiling.Filtered while hot is fallen copper sulfide precipitation.Column chromatography purification gets 2-(5-nitro-2-furyl)-1H-benzoglyoxaline-4-carboxylic acid.Productive rate about 65%.
Synthesizing of embodiment 3:2-(2-furyl)-1H-benzoglyoxaline-4-carboxylic acid
By example 2 method Synthetic 2s-(2-furyl)-1H-benzoglyoxaline-4-carboxylic acid, productive rate about 63%.
Embodiment 4-15:
Adopt different aldehydes X-CHO, by the series compound shown in the synthetic table 1 of example 2 methods,
Table 1
Figure A20091004505600192
Product structure is identified: Fig. 1 be embodiment 9 2-(2,3,4-trihydroxy-phenyl)-1H-benzoglyoxaline-4-carboxylic acid of preparing 1HNMR figure.Among the figure 1HNMR (DMSO, 400MHz) δ: 6.43-6.46 (d, 1H), 7.28-7.32 (t, 1H), 7.77-7.79 (d, 1H), 7.82-7.85 (m, 1H), 8.57 (s, 1H), 9.54 (s, 1H), 12.11 (s, 1H), 13.16 (s, 1H).
Embodiment 16:(L)-2-(5-nitro-2-furyl)-1H-benzoglyoxaline-4-(N-(1-methylol-2-p-nitrophenyl hydroxyethyl)) acid amides synthetic
2-(5-nitro-2-furyl)-1H-benzoglyoxaline-4-carboxylic acid is added in the sulfur oxychloride, and after reacting completely, with (L)-2-amino-1-p-nitrophenyl-1, ammediol (1.1eq) under agitation is added in the reaction solution.Stirring at room 2 hours filters out inorganic salt, and solvent evaporated obtains product 2-(5-nitro-2-furyl)-1H-benzoglyoxaline-4-(N-(1-methylol-2-p-nitrophenyl hydroxyethyl)) acid amides.Productive rate about 93%.
Product structure is identified:
1HNMR figure sees Fig. 2.
1HNMR(DMSO，400MHz)δ：3.59-3.60(m，1H)，3.65-3.67(t，1H)，4.16-4.22(q，1H)，5.07-5.08(t，1H)，5.27-5.28(t，1H)，6.16-6.17(d，1H)，7.35-7.39(t，1H)，7.53-7.54(d，1H)，7.72-7.75(m，2H)，7.77-7.79(m，2H)，8.00-8.01(d，1H)，8.05-8.07(d，3H)，10.04-10.06(d，2H)，14.05(s，1H)。
Synthesizing of embodiment 17:2-(5-nitro-2-furyl)-1H-benzoglyoxaline-4-(N-(1-methyl-2-rubigan hydroxyethyl))-acid amides
Take by weighing 2-(5-nitro-2-furyl)-1H-benzoglyoxaline-4-carboxylic acid and add sulfur oxychloride, reflux.After reaction finishes, 2-amino-1-rubigan-1-propyl alcohol (1.1eq) is dissolved in the tetrahydrofuran (THF), under agitation splashes into acyl chlorides.Stirring at room filters out inorganic salt, solvent evaporated, and product 2-(5-nitro-2-furyl)-1H-benzoglyoxaline-4-(N-(1-methylol-2-p-nitrophenyl hydroxyethyl)) acid amides can use column chromatography purification, productive rate about 92%.
Embodiment 18-36:
Adopt example 14 same technologies to synthesize the compound shown in the table 2.
Figure A20091004505600211
Table 2
Figure A20091004505600221
Product structure is identified (seeing Fig. 3-6):
Fig. 3 is (L)-2-(2-pyridyl)-1H-benzoglyoxaline-4-(N-(1-methylol-2-p-nitrophenyl hydroxyethyl)) acid amides of embodiment 21 preparation 1HNMR figure.Among the figure 1HNMR (DMSO, 400MHz) δ: 3.57-3.61 (m, 1H), 3.66-3.70 (m, 1H), 4.20-4.22 (m, 1H), 5.08-5.11 (q, 1H), 5.28-5.29 (d, 1H), and 6.29-6.30 (d, 1H), 7.28-7.32 (t, 1H), 7.57-7.61 (m, 1H), 7.67-7.73 (m, 4H), 8.02-8.06 (m, 3H), and 8.57-8.59 (m, 1H), 8.78-8.80 (m, 1H), 10.47-10.49 (d, 1H), 13.62 (s, 1H).
Fig. 4 is 2-(4-hydroxy phenyl)-1H-benzoglyoxaline-4-(the adjacent fluorophenyl of N-) acid amides of example 22 preparation 1HNMR figure.Among the figure 1HNMR (DMSO, 400MHz) δ: 6.95-6.99 (m, 2H), 7.11-7.17 (m, 1H), 7.22-7.26 (m, 1H), 7.34-7.39 (t, 1H), 7.40-7.44 (m, 1H), 7.74-7.76 (m, 1H), 7.94-7.96 (m, 1H), 8.13-8.16 (m, 2H), 8.64-8.68 (m, 1H), 10.17 (s, 1H), 12.63 (s, 1H), 13.31 (s, 1H).
Fig. 5 is (L)-2-(3-hydroxy phenyl)-1H-benzoglyoxaline-4-(N-(1-methylol-2-p-nitrophenyl hydroxyethyl)) acid amides of embodiment 23 preparation 1HNMR figure.Among the figure 1HNMR (DMSO, 400MHz) δ: 3.51-3.57 (m, 1H), 3.64-3.72 (m, 1H), 4.22-4.26 (m, 1H), and 5.05-5.08 (q, 1H), 5.25-5.27 (d, 1H), 6.16-6.18 (d, 1H), and 6.95-6.98 (d, 1H), 7.23-7.27 (t, 1H), 7.30-7.34 (t, 1H), and 7.36-7.40 (m, 1H), 7.65-7.73 (m, 4H), 7.80-7.84 (m, 1H), 8.03-8.10 (m, 2H), 9.76 (s, 1H), 10.43-10.46 (d, 1H), 13.31 (s, 1H).
Fig. 6 is 2-(5-nitro-2-furyl)-1H-benzoglyoxaline-4-(the adjacent fluorophenyl of N-) acid amides of embodiment 26 preparation 1HNMR figure.Among the figure 1HNMR (DMSO, 400MHz) δ: 7.13-7.19 (m, 1H), 7.23-7.27 (t, 1H), and 7.36-7.41 (t, 1H), 7.50-7.54 (m, 2H), and 7.85-7.87 (d, 1H), 7.94-7.95 (d, 1H), and 8.05-8.07 (d, 1H), 8.57-8.61 (t, 1H), 12.19-12.20 (d, 1H), 14.25 (s, 1H).

Claims (2)

1. benzoglyoxaline-4-acidamide type derivative is characterized in that structural formula is as follows:
Figure A2009100450560002C1
Wherein: X is alkyl, aryl or heterocyclic radical;
Y is hydrogen, alkyl, thiazolinyl, cycloalkyl, aryl or heterocyclic radical.
2. a kind of benzoglyoxaline according to claim 1-4-acidamide type derivative is characterized in that X and the Y in the structural formula is as follows:
X is:
Figure A2009100450560002C2
N=0-5 wherein,
R 1, R 2, R 3, R 4And R 5Be respectively H, CH 3, F, Cl, Br, I, OR 6, NO 2,
Figure A2009100450560003C1
Or
Figure A2009100450560003C2
R wherein 6Be H, CH 3Or CH 2CH 3, R 7And R 8Be respectively H, CH 3, CH 2CH 3Or CH 2CH 2OH, Ra 1, Ra 2, Ra 3, Ra 4And Ra 5Be respectively F, Cl, Br, I, CH 3, CH 2CH 3, ORa, CH 2CH 2OH, NO 2, N (Rb) 2, CN or COORc, wherein Ra is H, CH 3Or CH 2CH 3, Rb is H, CH 3, CH 2CH 3Or CH 2CH 2OH, Rc are H, CH 3, CH 2CH 3Or C 6H 5,
R 9, R 10, R 11, R 12And R 13Be respectively H, CH 3, CH 2CH 3, COOR 14, OR 15, CN, F, Cl, Br, I or N (R 16) 2, R wherein 14, R 15And R 16Be respectively H, CH 3Or CH 2CH 3,
R 17, R 18, R 19, R 20, R ' 17, R ' 18, R ' 19, R ' 20, R " 17, R " 18, R " 19And R " 20Be respectively H, CH 3, CH 2CH 3, OR 21, CF 3, CCl 3, CBr 3, N (R 22) 2, NO or NO 2, R wherein 21Be H, CH 3Or CH 2CH 3, R 22Be H, CH 3, CH 2CH 3Or CH 2CH 2OH,
R 23, R 24, R 25, R ' 23, R ' 24And R ' 25Be respectively H, CH 3, CH 2CH 3, F, Cl, Br, I, OR 26, NO 2, N (R 27) 2Or COOR 28, R wherein 26And R 28Be respectively H, CH 3, CH 2CH 3, R 27Be H, CH 3, CH 2CH 3, CH 2CH 2OH,
R 29, R 30, R 31And R 32Be respectively H, CH 3, CH 2CH 3, OCH 3, CH 2OH, NO 2Or N (R 33) 2, R wherein 33Be respectively H, CH 3, CH 2CH 3Or CH 2CH 2OH,
R 34And R 36Be respectively H, (CH 2) nCH 3, CH 2OH, C H 2CH 2OH, CH (CH 3) 2Or CH 2CH (OH) CH 3, n= 0-5, R 35, R 37And R 38Be respectively H, CH 3, CH 2CH 3, OCH 3, CH 2OH, NO 2Or N (R ' 33) 2, R ' wherein 33Be H, CH 3, CH 2CH 3Or CH 2CH 2OH,
R 39, R 40, R 42And R 43Be respectively H, CH 3, CH 2CH 3, OCH 3, CH 2OH, NO 2Or N (R " 33) 2, R wherein " 33Be H, CH 3, CH 2CH 3Or CH 2CH 2OH, R 41Be H, (CH 2) nCH 3, CH 2OH, CH 2CH 2OH or CH 2CH (OH) CH 3, n=0-5,
Z is N, O, S, R 44, R 45, R 46, R ' 44, R ' 45And R ' 46Be respectively H, CH 3, CH 2CH 3, OR 47, NO 2, N (R 48) 2, CN or COOR 49, R wherein 47And R 49Be respectively H, CH 3Or CH 2CH 3, R 48Be H, CH 3, CH 2CH 3Or CH 2CH 2OH,
Rs 1, Rs 2, R ' s 1And R ' s 2Be respectively H, CH 3, CH 2CH 3, N (R ') 2, F, Cl, Br, I or NHCOR ", wherein R ' is H, CH 3, CH 2CH 3Or CH 2CH 2OH, R " is CH 3, CH 2CH 3Or C 6H 5,
Rm 1, Rm 2, Rm 3, R ' m 1, R ' m 2Or R ' m 3Be H, CH 3, CH 2CH 3, F, Cl, Br, OH, N (Rm) 2Or C 6H 5, wherein Rm is H, CH 3, CH 2CH 3, CH 2CH 2OH;
Y is
Figure A2009100450560003C3
Wherein
R 50, R 51, R 52, R 53, R 54, R 55, R 56, R 57, R 58, R 59, R 60, R 61, R 62, R 63, R 64, R 65, R 66, R 67, R 68, R 69, R 70, R 71, R 72And R 73Be respectively H, CH 3, CH 2CH 3, CH 2OH, OR 74, CN, NO 2, N (R 75) 2, F, Cl, Br or
Figure A2009100450560004C1
R wherein 74Be H, CH 3Or CH 2CH 3, R 75Be H, CH 3, CH 2CH 3Or CH 2CH 2OH, R 76Be respectively H, CH 3, OH, NO 2, NH 2,
R 77, R 78, R 79, R 80And R 81Be respectively H, CH 3, CH 2CH 3, OR 82, NO 2, CN, COOR 83, F, Cl, Br, CF 3, CCl 3, N (R 84) 2, R wherein 82And R 83Be respectively H, CH 3, CH 2CH 3, R 84Be H, CH 3, CH 2CH 3, CH 2CH 2OH,
R 85, R 86And R 87Be respectively H, CH 3, CH 2CH 3, OH or NH 2,
Q is N, O or S, R 88, R 89, R 90, R ' 88, R ' 89And R ' 90Be respectively H, CH 2CH 3, OR 91, NO 2, N (R 92) 2, CN, COOR 93, R wherein 91And R 93Be respectively H, CH 3, CH 2CH 3, R 92Be H, CH 3, CH 2CH 3Or CH 2CH 2OH,
R 94, R 95, R ' 94And R ' 95Be respectively H, CH 3, CH 2CH 3, N (R 96) 2, F, Cl, Br, I or NHCOR 97, R wherein 96Be H, CH 3, CH 2CH 3Or CH 2CH 2OH, R 97Be CH 3, CH 2CH 3Or C 6H 5
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